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Novel synthetic strategies for the construction of lipopeptide vaccines using carbohydrate scaffolds
5th Asia Pacific Global Summit and Expo on Vaccines & Vaccination
July 27-29, 2015 Brisbane, Australia

Pavla Simerska

Posters-Accepted Abstracts: J Vaccines Vaccin

Abstract:

The goal of this project was to develop methodologies for the construction of self-aduvanting carbohydrate-core lipopeptide vaccines containing multiple copies of immunogenic peptide antigens. The lipidic sequence imparted self-aduvanting properties and the carbohydrate core was varied to determine the optimum orientation of the antigens. The group A streptococcal (GAS) infection was chosen as a model disease, and therefore different GAS B-cell peptide antigens were incorporated into our vaccine system. In order to be able to quickly and efficiently construct libraries of vaccine candidates, a convergent strategy was developed where-by building blocks could be synthesised and purified prior to final assembly. An efficient and convenient synthesis of a highly versatile alkyne functionalised carbohydrate building block and lipidated Fmoc-lysine were devised. The carbohydrate building block was coupled to the lipidic moiety (three lipidated Fmoc-lysines) on solid support, and allowed for the conjugation of four copies of purified GAS peptide antigens using the alkyne-azide Huisgen cycloaddition click reaction. Since each component was synthesised and purified before final assembly, the purity of the final vaccine constructs was significantly improved, hence final purification was less demanding. The strategy was elaborated by the preparation of a vaccine candidate which incorporated an additional promiscuous T-helper epitope. Although B cells may be activated via a number of T cell-independent routes, the T cell-dependent activation of B cells can lead to stronger and more long-term immune responses. In vitro and in vivo methods were used to evaluate structure activity relationship of the carbohydrate-core lipopeptide GAS vaccines.